Arterioles, as described herein, are vessels in the arterial circulation (as opposed to the venous circulation) with a diameter (after perfusion fixation or in vivo) of <200 μM. There is an extensive literature on changes in arterioles associated with hypertension, aging, subarachnoid hemorrhage, multi-infarct dementia, Alzheimer's disease, and chronic kidney disease as well as in other conditions. It appears that a variety of pathological conditions can result in thickening of these arterioles accompanied by a loss of normal vasoreactivity.
The normal response to a fall in blood pressure is vasodilation to allow resistance to decrease and maintain forward flow. Failure to be able to vasodilate arterioles in the face of a fall in blood pressure may result in a fall in blood flow to the target organ. If the target organ is the brain, the fall in forward blood flow can result in an infarct in the region of the arterioles involved.
Since the arterioles are so small they ordinarily serve a small area of the brain and therefore the infarct is small and may only be perceived as a “Senior Moment”. However, we believe the accumulation of such a series of insults over time may lead to significant end organ damage.
The major treatments for prevention of such end organ damage include blood pressure control and control of plasma glucose and lipid levels. The use of certain agents (e.g., statins) to improve the structure and function of small to large arteries has been known and assumed to relate to the ability of these agents to lower cholesterol and reduce inflammatory cell infiltration into the arteries (see, e.g., Schonbeck et al. (2004) Circulation 109(21 Suppl 1): II18-26).